| Gene (symbol) | Evidence for AD-dHMN association (study + year) | Example pathogenic/likely pathogenic variant(s) mentioned in evidence | Mechanistic category | Key clinical notes (phenotype highlights) | Notes/limitations |
|---|---|---|---|---|---|
| NARS1 | Theuriet et al., 2024 reported a previously unreported heterozygous NARS1 variant segregating with dominant dHMN in a French family (pqac-00000017) | c.1555G>C, p.(Gly519Arg) (heterozygous); functional yeast complementation supported loss of function (pqac-00000017) | Aminoacyl-tRNA synthetase | Distal weakness, osteoarticular deformities, pure motor neuropathy on NCS/EMG, brisk reflexes/possible UMN involvement; patients remained ambulatory, suggesting slowly progressive disease (pqac-00000017) | Strong recent AD-dHMN-specific evidence, but based on one family in the available snippet; variant absent from population databases in report (pqac-00000017) |
| GARS1 | Xie et al., 2020 identified novel heterozygous GARS variants with typical dHMN-V phenotype and concluded ARS genes may be frequent causes of AD-dHMN; Carroll 2019 lists AD-dHMN-GARS / HMN5A (pqac-00000001, pqac-00000028) | c.373G>C p.E125Q; c.1015G>A p.G339R; also GARS listed as AD-dHMN gene in classification table (pqac-00000001, pqac-00000028) | Aminoacyl-tRNA synthetase | Typical dHMN-V with upper-limb predominance/hand wasting in classification framework; overlaps with axonal CMT phenotypes (pqac-00000001, pqac-00000028) | AD association is well supported in available evidence, but phenotype overlaps with CMT2D and exact variant-specific expressivity varies (pqac-00000001, pqac-00000028) |
| HSPB1 | Carroll 2019 lists HMN2B as AD-dHMN-HSPB1; Lupo 2016 reviews HSPB1 as one of the main dHMN chaperone genes with ~30 reported mutations (pqac-00000028, pqac-00000007) | No specific HSPB1 nucleotide/protein variant named in the available snippets used here (pqac-00000007, pqac-00000028) | Chaperone / proteostasis (small heat-shock protein) | Canonical AD-dHMN form in modern classification; hereditary motor neuropathy with distal weakness/atrophy and little sensory involvement (pqac-00000028, pqac-00000007) | Gene-disease association is established, but this evidence subset does not provide a named variant or variant-level phenotype details (pqac-00000007, pqac-00000028) |
| HSPB8 | Carroll 2019 lists HMN2A as AD-dHMN-HSPB8; Lupo 2016 reviews HSPB8 as a dHMN chaperone gene and notes many cases affect residue K141 (pqac-00000028, pqac-00000007) | Mutations affecting K141 residue (specific substitutions not detailed in the snippet) (pqac-00000007) | Chaperone / proteostasis (small heat-shock protein) | Classified AD-dHMN form; motor-predominant distal neuropathy with overlap across neuromuscular phenotypes (pqac-00000028, pqac-00000007) | Variant examples are only residue-level in the available evidence; more granular pathogenicity data are not given in retrieved snippets (pqac-00000007, pqac-00000028) |
| HSPB3 | Carroll 2019 lists HMN2C as AD-dHMN-HSPB3; Lupo 2016 notes HSPB3 is a rare dHMN chaperone gene with only one mutation described at that time (pqac-00000028, pqac-00000007) | No specific variant named in the available snippets (pqac-00000007, pqac-00000028) | Chaperone / proteostasis (small heat-shock protein) | Rare AD-dHMN subtype in classification framework (pqac-00000028) | Association is supported by classification/review evidence, but variant-level and phenotype-detail evidence are sparse in available snippets (pqac-00000007, pqac-00000028) |
| BSCL2 | Carroll 2019 lists HMN5C as AD-dHMN-BSCL2 and links it to Silver syndrome/CMT overlap; Zambon 2023 gene table includes BSCL2 among dominant HMN/dHMN-associated genes (pqac-00000028, pqac-00000030) | No specific BSCL2 variant named in the cited snippets used for this table (pqac-00000028, pqac-00000030) | ER / lipid droplet biology; often grouped with ER-related motor neuropathy mechanisms | AD-dHMN form with overlap syndromes including Silver syndrome and CMT2D-like features (pqac-00000028) | AD association is clear in classification tables, but no variant-specific details are available in the retrieved evidence subset here (pqac-00000028, pqac-00000030) |
| REEP1 | Carroll 2019 lists HMN5B as AD-dHMN-REEP1 and notes pyramidal signs; Wu 2022 reported truncating/splice REEP variants associated with distal motor neuropathy plus pyramidal signs (pqac-00000028, pqac-00000029) | c.337C>T p.R113*; c.417+1G>A (pqac-00000029) | ER shaping / membrane modeling | Distal motor neuropathy with pyramidal signs; overlap with hereditary spastic paraplegia spectrum (pqac-00000028, pqac-00000029) | Evidence supports AD-dHMN classification, but available cohort snippet emphasizes broader motor neuropathy/plus phenotypes rather than pure dHMN only (pqac-00000028, pqac-00000029) |
| DCTN1 | Zambon 2023 gene table includes DCTN1 among genes associated with dominant hereditary motor neuronopathy/dHMN spectrum (pqac-00000030) | No specific DCTN1 variant named in the available snippet used here (pqac-00000030) | Axonal transport / dynein-dynactin pathway | Included in dominant motor neuronopathy gene table; relevant to distal hereditary motor neuropathy overlap spectrum (pqac-00000030) | Available evidence confirms table inclusion but lacks variant-level and phenotype-detail data in retrieved snippets (pqac-00000030) |
| BICD2 | Frasquet 2021 found BICD2 to be a relatively common gene in a dHMN cohort (8.0% of patients), but AD inheritance is not explicitly stated in the cited snippet; included here as requested with caution (pqac-00000003, pqac-00000026) | No specific BICD2 variant named in the cited evidence used here (pqac-00000003, pqac-00000026) | Axonal transport / dynein adaptor | Associated with dHMN spectrum, including non-length-dependent/SMALED overlap in broader literature context of cohort (pqac-00000003, pqac-00000026) | Inheritance is mixed/unspecified in available snippets; AD assignment should be treated cautiously unless confirmed from a dedicated source (pqac-00000003, pqac-00000026) |
| DNAJB2 | Lupo 2016 reviews DNAJB2 as a dHMN chaperone gene, but emphasizes founder c.352+1G>A cases and does not establish AD inheritance in the available snippet; Frasquet 2021 found DNAJB2 variants in 6.7% of patients (pqac-00000007, pqac-00000003) | Founder c.352+1G>A mentioned in review (pqac-00000007) | Chaperone / proteostasis (HSP40 co-chaperone) | dHMN-associated motor neuropathy gene in cohort/review evidence (pqac-00000007, pqac-00000003) | Important dHMN gene, but AD inheritance is not certain in the available evidence and may vary; included only with this limitation noted (pqac-00000007, pqac-00000003) |


*Table: This table summarizes genes with available evidence for autosomal dominant distal hereditary motor neuropathy, highlighting example variants, mechanism classes, and phenotype notes. It is useful for quickly linking genotype, disease mechanism, and the strength or limitations of the available evidence.*